99 - systemic lupus erythematosus ( SLE )

Systemic lupus erythematosus (SLE or lupus) is a chronic autoimmune disease that can be fatal, though with recent medical advances, fatalities are becoming increasingly rare. As with other autoimmune diseases, the immune system attacks the body’s cells and tissue, resulting in inflammation and tissue damage. SLE can affect any part of the body, but most often harms the heart, joints, skin, lungs, blood vessels, liver, kidneys and nervous system. The course of the disease is unpredictable, with periods of illness (called flares) alternating with remission. Lupus can occur at any age, and is most common in women, particularly of non-European descent.^[1] Lupus is treatable symptomatically, mainly with corticosteroids and immunosuppressants, though there is currently no cure. Survival in patients with SLE in the United States, Canada, Europe, and China is approximately 95% at 5 years, 90% at 10 years, and 78% at 20 years.^[2]

Classification

Lupus is a chronic autoimmune disease. Clinically, it can affect multiple organ systems including the heart, skin, joints, kidneys and nervous system. There are several types of lupus; generally when the word 'lupus' alone is used, it refers to the systemic lupus erythematosus or SLE as discussed in this article. Other types include:

• Drug-induced lupus erythematosus, a drug-induced form of SLE; this type of lupus can occur equally for either gender
• Lupus nephritis, an inflammation of the kidneys caused by SLE
• Discoid lupus erythematosus, a skin disorder which causes a red, raised rash on the face, scalp or rest of the body, which occasionally (1-5%) develops into SLE^[3]
• Subacute cutaneous lupus erythematosus, which causes non-scarring skin lesions on patches of skin exposed to sunlight^[4]
• Neonatal lupus, a rare disease affecting babies born to women with SLE, Sjögren's syndrome or sometimes no autoimmune disorder. It is theorized that maternal antibodies attack the fetus, causing skin rash, liver problems, low blood counts (which gradually fade) and heart block leading to bradycardia.^[4]

Signs and symptoms

SLE is one of several diseases known as "the great imitators" ^[5] because its symptoms vary so widely it often mimics or is mistaken for other illnesses, and because the symptoms come and go unpredictably. Diagnosis can be elusive, with patients sometimes suffering unexplained symptoms and untreated SLE for years. Common initial and chronic complaints are fever, malaise, joint pains, myalgias and fatigue. Because they are so often seen with other diseases, these signs and symptoms are not part of the diagnostic criteria for SLE. When occurring in conjunction with other signs and symptoms (below), however, they are considered suggestive.

Common symptoms explained

Dermatological manifestations

As many as 30% of patients present with some dermatological symptoms (and 65% suffer such symptoms at some point), with 30% to 50% suffering from the classic malar rash (or butterfly rash) associated with the disease. Patients may present with discoid lupus (thick, red scaly patches on the skin). Alopecia, mouth, nasal, and vaginal ulcers, and lesions on the skin are also possible manifestations.

Musculoskeletal manifestations

Patients most often seek medical attention for joint pain, with small joints of the hand and wrist usually affected, although any joint is at risk. The Lupus Foundation of America "estimates more than 90 percent will experience joint and/or muscle pain at some time during the course of their illness".^[6] Unlike rheumatoid arthritis, lupus arthritis is less disabling and it usually does not cause severe destruction of the joints. Fewer than 10 percent of people with lupus arthritis will develop deformities of the hands and feet.^[6]

Hematological manifestations

Anemia and iron deficiency may develop in as many as half of patients. Low platelet and white blood cell counts may be due to the disease or a side-effect of pharmacological treatment. Patients may have an association with antiphospholipid antibody syndrome (a thrombotic disorder) where autoantibodies to phospholipids are present in the patient's serum. Abnormalities associated with antiphospholipid antibody syndrome include a paradoxical prolonged PTT (which usually occurs in hemorrhagic disorders) and a positive test for antiphospholipid antibodies; the combination of such findings have earned the term "lupus anticoagulant positive". Another autoantibody finding in lupus is the anticardiolipin antibody which can cause a false positive test for syphilis.

Cardiac manifestations

Patients may present with inflammation of various parts of the heart, such as pericarditis, myocarditis, and endocarditis. The endocarditis of SLE is characteristically non-infective (Libman-Sacks endocarditis) and involves either the mitral valve or the tricuspid valve. Atherosclerosis also tends to occur more often and advance more rapidly in SLE patients than in the general population.^[7][8][9]

Pulmonary manifestations

Lung and pleura inflammation can cause pleuritis, pleural effusion, lupus pneumonitis, chronic diffuse interstitial lung disease, pulmonary hypertension, pulmonary emboli, pulmonary hemorrhage.

Hepatic involvement

See autoimmune hepatitis

Renal involvement

Painless hematuria or proteinuria may often be the only presenting renal symptom. Acute or chronic renal impairment may develop with lupus nephritis, leading to acute or end stage renal failure. Because of early recognition and management of SLE, end stage renal failure occurs in less than 5% of patients.

Histologically, a hallmark of SLE is membranous glomerulonephritis with "wire loop" abnormalities.^[10] This finding is due to immune complex deposition along the glomerular basement membrane leading to a typical granular appearance in immunofluorescence testing.

Neurological manifestations

About 10% of patients may present with seizures or psychosis. A third may test positive for abnormalities in the cerebrospinal fluid.

T-cell abnormalities

Abnormalities in T cell signaling are associated with SLE, including deficiency in CD45 phosphatase and increased expression of CD40 ligand.

Other rarer manifestations

lupus gastroenteritis, lupus pancreatitis, lupus cystitis, autoimmune inner ear disease, parasympathetic dysfunction, retinal vasculitis, and systemic vasculitis.

Other abnormalities include:

• Increased expression of FcεRIγ, which replaces the sometimes deficient TCR ζ chain
• Increased and sustained calcium levels in T cells
• Moderate increase of inositol triphosphate
• Reduction in PKC phosphorylation
• Reduction in Ras-MAP kinase signaling
• Deficiencies in protein kinase A I activity

Causes

In SLE, the body's immune system produces antibodies against itself, particularly against proteins in the cell nucleus. SLE is triggered by environmental factors which are unknown (but probably include viruses), in people with certain combinations of genes in their immune system.

"All the key components of the immune system are involved in the underlying mechanisms" of SLE, according to Rahman, and SLE is the prototypical autoimmune disease. The immune system must have a balance (homeostasis) between being sensitive enough to protect against infection, and being too sensitive and attacking the body's own proteins (autoimmunity). From an evolutionary perspective, according to Crow, the population must have enough genetic diversity to protect itself against a wide range of possible infection, and some genetic combinations result in autoimmunity. The likely environmental triggers include ultraviolet light, drugs, and viruses. These stimuli cause the destruction of cells, and expose their DNA, histones, and other proteins, particularly parts of the cell nucleus. Because of genetic variations in different components of the immune system, in some people the immune system attacks these nuclear-related proteins and produces antibodies against them. Ultimately, these antibody complexes damage blood vessels, in critical areas of the body such as the glomeruli of the kidney. These antibody attacks are the cause of SLE. Researchers are now identifying the individual genes, the proteins they produce, and their role in the immune system. Each protein is a link on the autoimmune chain, and researchers are trying to find drugs to break each of those links.

SLE is a chronic inflammatory disease believed to be a type III hypersensitivity response with potential type II involvement,

Genetics

The first mechanism may arise genetically. Research indicates that SLE may have a genetic link. Lupus does run in families, but no single "lupus gene" has yet been identified. Instead, multiple genes appear to influence a person's chance of lupus developing when triggered by environmental factors. The most important genes are located on chromosome 6, where mutations may occur randomly (de novo) or be inherited. Additionally, people with SLE have an altered RUNX-1 binding site, which may be either cause or contributor (or both) to the condition. Altered binding sites for RUNX-1 have also been found in people with psoriasis and rheumatoid arthritis.

Environmental triggers

The second mechanism may be due to environmental factors. These factors may not only exacerbate existing lupus conditions, but also trigger the initial onset. They include certain medications (such as some antidepressants and antibiotics), extreme stress, exposure to sunlight, hormones, and infections. Some researchers have sought to find a connection between certain infectious agents (viruses and bacteria), but no pathogen can be consistently linked to the disease. UV radiation has been shown to trigger the photosensitive lupus rash, but some evidence also suggests that UV light is capable of altering the structure of the DNA, leading to the creation of autoantibodies. Some researchers have found that women with silicone gel-filled breast implants have produced antibodies to their own collagen, but it is not known how often these antibodies occur in the general population and there is no data that show these antibodies cause connective tissue diseases such as lupus.

Drug reactions

Drug-induced lupus erythematosus is a reversible condition that usually occurs in patients being treated for a long-term illness. Drug-induced lupus mimics systemic lupus. However, symptoms of drug-induced lupus generally disappear once a patient is taken off the medication which triggered the episode. There are about 400 medications currently in use that can cause this condition, though the most common drugs are procainamide, hydralazine and quinidine.

Non-SLE forms of lupus

Discoid (cutaneous) lupus is limited to skin symptoms and is diagnosed via biopsy of skin rash on the face, neck or scalp. Often an anti-nuclear antibody (ANA) test for discoid patients is negative or a low-titre positive. About 1-5% of discoid lupus patients eventually develop SLE.

Clearance deficiency

Clearance deficiency

The exact mechanisms for the development of systemic lupus erythematosus (SLE) are still unclear since the pathogenesis is a multifactorial event. Beside discussed causations, impaired clearance of dying cells is a potential pathway for the development of this systemic autoimmune disease. This includes deficient phagocytic activity, scant serum components in addition to increased apoptosis.

Monocytes isolated from whole blood of SLE patients show reduced expression of CD44 surface molecules involved in the uptake of apoptotic cells. Most of the monocytes and tingible body macrophages (TBM), which are found in the germinal centres of lymph nodes, even show a definitely different morphology in patients with SLE. They are smaller or scarce and die earlier. Serum components like complement factors, CRP and some glycoproteins are furthermore decisively important for an efficiently operating phagocytosis. In patients these components are often missing, diminished or inefficient.

The clearance of early apoptotic cells is an important function in multicellular organisms. It leads to a progression of the apoptosis process and finally to secondary necrosis of the cells, if this ability is disturbed. Necrotic cells release nuclear fragments as potential autoantigens as well as internal danger signals, inducing maturation of dendritic cells (DC), since they have lost their membranes integrity. Increased appearance of apoptotic cells also is simulating inefficient clearance. That leads to maturation of DC and also to the presentation of intracellular antigens of late apoptotic or secondary necrotic cells, via MHC molecules. Autoimmunity possibly results by the extended exposure to nuclear and intracellular autoantigens derived from late apoptotic and secondary necrotic cells. B and T cell tolerance for apoptotic cells is abrogated and the lymphocytes get activated by these autoantigens; inflammation and the production of autoantibodies by plasma cells is initiated. A clearance deficiency in the skin for apoptotic cells has also been observed in patients with cutaneous lupus erythematosus (CLE).

germinal centres

Accumulation in germinal centres (GC)

In healthy conditions apoptotic lymphocytes are removed in germinal centres by specialised phagocytes, the tingible body macrophages (TBM); that’s why no free apoptotic and potential autoantigenic material can be seen. In some patients with SLE accumulation of apoptotic debris can be observed in GC, because of an ineffective clearance of apoptotic cells. In close proximity to TBM, follicular dendritic cells (FDC) are localised in GC, which attach antigen material to their surface and in contrast to bone marrow-derived DC, neither take it up nor present it via MHC molecules. Autoreactive B cells can accidentally emerge during somatic hypermutation and migrate into the GC light zone. Autoreactive B cells, maturated coincidently, normally don’t receive survival signals by antigen planted on follicular dendritic cells and perish by apoptosis. In the case of clearance deficiency apoptotic nuclear debris accumulates in the light zone of GC and gets attached to FDC. This serves as a germinal centre survival signal for autoreactive B-cells. After migration into the mantle zone autoreactive B cells require further survival signals from autoreactive helper T cells, which promote the maturation of autoantibody producing plasma cells and B memory cells. In the presence of autoreactive T cells a chronic autoimmune disease may be the consequence.

Pathophysiology

One manifestation of lupus is abnormalities in apoptosis, a type of programmed cell death in which aging or damaged cells are neatly disposed of as a part of normal growth or functioning.

Abnormalities in apoptosis

• Apoptosis is increased in monocytes and keratinocytes
• Expression of Fas by B cells and T cells is increased
• There are correlations between the apoptotic rates of lymphocytes and disease activity

Tingible body macrophages (TBMs) are large phagocytic cells in the germinal centers of secondary lymph nodes. They express CD68 protein. These cells normally engulf B cells which have undergone apoptosis after somatic hypermutation. In some patients with SLE, significantly fewer TBMs can be found, and these cells rarely contain material from apoptotic B cells. Also, uningested apoptotic nuclei can be found outside of TBMs. This material may present a threat to the tolerization of B cells and T cells. Dendritic cells in the germinal center may endocytose such antigenic material and present it to T cells, activating them. Also, apoptotic chromatin and nuclei may attach to the surfaces of follicular dendritic cells and make this material available for activating other B cells which may have randomly acquired self-specificity through somatic hypermutation.^[15]

Diagnosis

Microphotograph of a histological section of human skin prepared for direct immunofluorescence using an anti-IgG antibody. The skin is from a patient with systemic lupus erythematosus and shows IgG deposit at two different places : the first is a band-like deposit along the epidermal basement membrane ("lupus band test" is positive), the second is within the nuclei of the epidermal cells (anti-nuclear antibodies are present).

Some physicians make a diagnosis on the basis of the ACR classification criteria (see below). The criteria, however, were established mainly for use in scientific research (i.e. inclusion in randomized controlled trials), and patients may have lupus but never meet the full criteria.

Anti-nuclear antibody testing and anti-extractable nuclear antigen (anti-ENA) form the mainstay of serologic testing for lupus. Antiphospholipid antibodies occur more often in SLE, and can predispose for thrombosis. More specific are the anti-smith and anti-dsDNA antibodies. Other tests routinely performed in suspected SLE are complement system levels (low levels suggest consumption by the immune system), electrolytes and renal function (disturbed if the kidney is involved), liver enzymes and a complete blood count.

Formerly, the lupus erythematosus (LE) cell test was used for diagnosis, however those LE cells are only found in 50-75% of SLE patients, and are also found in some patients with rheumatoid arthritis, scleroderma, and drug sensitivities. Because of this, the LE cell test is now performed only rarely and is mostly of historical significance.^[16]

Diagnostic criteria

The American College of Rheumatology (ACR) has established eleven criteria in 1982,^[17] which were revised in 1997^[18] as a classificatory instrument to operationalise the definition of SLE in clinical trials. They were not intended to be used to diagnose individual patients and do not do well in that capacity. For inclusion in clinical trials, patients must meet the following three criteria to be classified as having SLE: (i) patient must present with four of the below eleven symptoms (ii) either simultaneously or serially (iii) during a given period of observation.

1. Serositis: Pleuritis (inflammation of the membrane around the lungs) or pericarditis (inflammation of the membrane around the heart)sensitivity = 56%; specificity = 86% (pleural is more sensitive; cardiac is more specific)^[19]
2. Oral ulcers: include oral or nasopharyngeal ulcers
3. Arthritis: nonerosive arthritis of two or more peripheral joints, with tenderness, swelling or effusionsensitivity = 86%; specificity = 37%^[19]
4. Photosensitivity (exposure to ultraviolet light causes rash). sensitivity = 43%; specificity = 96%^[19]
5. Hematologic disorder: Hemolytic anemia (low red blood cell count) or leukopenia (white blood cell count<4000/ul), sensitivity =" 59%;" specificity =" 89%[19] Hypocomplementemia is also seen, due to either consumption of C3 and C4 by immune complex-induced inflammation, or to congenitally complement deficiency, which may predispose to SLE.
6. Renal disorder: More than 0.5 g per day protein in urine, or cellular casts seen in urine under a microscope.sensitivity = 51%; specificity = 94%^[19]
7. Anti-nuclear antibody test positive. sensitivity = 99%; specificity = 49%^[19]
8. Immunologic disorder: Positive anti-Sm, anti-ds DNA, anti-phospholipid antibody and/or false positive serological test for syphilis. sensitivity = 85%; specificity = 93%^[19]. Presence of anti-ss DNA in 70% of patients (though also positive in patients with rheumatic disease and healthy persons^[20])
9. Neurologic disorder: Seizures or psychosis. sensitivity = 20%; specificity = 98%^[19]
10. Malar rash (rash on cheeks). sensitivity = 57%; specificity = 96%^[19]
11. Discoid lupus (red, scaly patches on skin which cause scarring) sensitivity = 18%; specificity = 99%^[19]

A useful mnemonic for these 11 criteria is SOAP BRAIN MD: Serositis (8), Oral ulcers (4), Arthritis (5), Photosensitivity (3), Blood Changes (9), Renal involvement (proteinuria or casts) (6), ANA (10), Immunological changes (11), Neurological signs (seizures, frank psychosis) (7), Malar Rash (1), Discoid Rash (2).

Some patients, especially those with antiphospholipid syndrome, may have SLE without four criteria and SLE is associated with manifestations other than those listed in the criteria.^[21][22][23]

Alternative criteria

Recursive partitioning has been used to identify more parsimonious criteria.^[19] This analysis presented two diagnostic classification trees:

1. Simplest classification tree: LSE is diagnosed if the patient has an immunologic disorder (anti-DNA antibody, anti-Smith antibody, false positive syphilis test, or LE cells) or malar rash.

• sensitivity = 92%
• specificity = 92%

2. Full classification tree: Uses 6 criteria.

• sensitivity = 97%
• specificity = 95%

Other alternative criteria have been suggested.^[24]

Common misdiagnoses

Porphyria

Porphyrias are complex genetic disorders that share many symptoms with lupus, but impact the enzymes responsible for building heme, a component needed in heme proteins. Porphyrias are ecogenic disorders requiring both environmental and genetic backgrounds to manifest with a variety of symptoms and medical complications. They are noted for photosensitivity and have been associated with transient and permanent production of autoantibodies. The five major forms of dominantly inherited porphyrias (acute intermittent porphyria, porphyria cutanea tarda, hereditary coproporphyria, variegate porphyria and erythropoietic protoporphyria) have been detected in systemic lupus erythematosus and discoid lupus patients over the past 50 years. Physicians should have a high degree of suspicion of porphyrias in all lupus cases and act accordingly when patients are in a medical crisis that may be due to an underlying acute hepatic porphyria. Drug-induced lupus and photosensitivity warrant an investigation for an underlying porphyria since multiple drug reactions are a hallmark complication of porphyrias. Patients with both lupus and porphyrias should avoid porphyrinogenic drugs and hormone preparations.

Patients with acute hepatic porphyrias (acute intermittent porphyria, hereditary coproporphyria, variegate porphyria) have been detected in lupus patients with severe life-threatening "lupus" complications known as neurolupus. Symptoms are identical to acute hepatic porphyria attacks and include seizures, psychosis, peripheral neuropathy and syndrome of inappropriate antidiuretic hormone (SIADH) associated with dangerously low sodium levels (hyponatremia). Porphyria attacks require intervention with intravenous glucose, heme preparations and the discontinuation of dangerous porphyrinogenic drugs including antiseizure drugs. Several other lupus complications have been associated with porphyrias including pancreatitis and pericarditis. Porphyrin testing should be performed on urine, stool/bile and blood to detect all types of porphyrias, and repeat testing should be performed in suspicious cases. Appropriate enzyme tests or DNA testing should also be pursued to obtain a complete diagnosis which could include a dual porphyria.

Common dual diagnoses

SLE is sometimes diagnosed in conjunction with other conditions, including Rheumatoid Arthritis, Scurvy and Fibromyalgia...

Treatment

As lupus erythematosus is a chronic disease with no known cure, treatment is restricted to dealing with the symptoms; essentially this involves preventing flares and reducing their severity and duration when they occur. There are several means of preventing and dealing with flares, including drugs, alternative medicine and lifestyle changes.

Drug therapy

Due to the variety of symptoms and organ system involvement with Lupus patients, the severity of the SLE in a particular patient must be assessed in order to successfully treat SLE. Mild or remittent disease can sometimes be safely left untreated. If required, non-steroidal anti-inflammatory drug and anti-malarials may be used.

Disease-modifying antirheumatic drugs (DMARDs) are used preventively to reduce incidence of flares, the process of the disease, and lower the need for steroid use; when flares occur, they are treated with corticosteroids. DMARDs commonly in use are anti-malarials and immunosuppressants (e.g. methotrexate and azathioprine). Hydroxychloroquine (trade name Plaquenil) is an FDA approved anti-malarial used for constitutional, cutaneous, and articular manifestations, while Cyclophosphamide (trade names Cytoxan and Neosar) is used for severe glomerulonephritis or other organ-damaging complications, and in 2005, mycophenolic acid (trade name CellCept) became accepted for treatment of lupus nephritis.

In more severe cases, medications that modulate the immune system (primarily corticosteroids and Immunosuppresive drug immunosuppressants) are used to control the disease and prevent recurrence of symptoms (known as flares). Patients who require steroids frequently may develop obesity, diabetes mellitus diabetes and osteoporosis. Depending on the dosage, corticosteroids can cause other side effects such as a puffy face, an unusually large appetite and difficulty sleeping. Those side effects can subside if and when the large initial dosage is reduced, but long term use of even low doses can cause elevated blood pressure and cataracts. Due to these side effects, steroids are avoided if possible.

Since a large percentage of Lupus patients suffer from varying amounts of chronic pain, stronger prescription analgesics may be used if over-the-counter drugs, mainly non-steroidal anti-inflammatory drug do not provide effective relief. Moderate pain in Lupus patients if typically treated with mild prescription opiates such as Dextropropoxyphene (trade name Darvocet), and Co-codamol (trade name Tylenol #3). Moderate to severe chronic pain is treated with stronger opioids such as Hydrocodone (trade names Lorcet, Lortab, Norco, Vicodin, Vicoprofen) or longer-acting continuous release opioids such as Oxycodone (trade names OxyContin), MS Contin, or Methadone. The Fentanyl Duragesic Transdermal patch is also a widely-used treatment option for chronic pain due to Lupus complications because of its long-acting timed release and easy usage. When opioids are used for prolonged periods drug tolerance, chemical dependency and (rarely) addiction may occur. Opiate addiction is not typically a concern for Lupus patients, since the condition is not likely to ever completely disappear. Thus, lifelong treatment with opioids is fairly common in Lupus patients that exhibit chronic pain symptoms; accompanied by periodic titration that is typical of any long-term opioid regimen.

UVA1 phototherapy

In 1987, Tina Lomardi, MD first reported that long-wave ultraviolet radiation (UVA1) had a favorable effect on disease activity in SLE model mice. Several clinicals trials investigating this new, counter-intuitive therapeutic approach, conducted by both McGrath and independent Dutch searchers, have confirmed these findings in SLE patients. ^[25] Devices for administering therapeutic doses of UVA1 are available in Europe but not in the U.S. However, the U.S. Food and Drug Administration Office of Science and Technology conducted UVA1 phototherapy studies in an SLE mouse model in 1997 "to prepare for future reviews of UVA-emitting tanning devices for such clinical applications".

Lifestyle changes

Other measures such as avoiding sunlight or covering up with sun protective clothing can also be effective in preventing problems due to photosensitivity. Weight loss is also recommended in overweight and obese patients to alleviate some of the effects of the disease, especially where joint involvement is significant.

Treatment research

Other immunosuppressants (drugs that lower the body's normal immune response) and bone marrow transplant autologous stem cell transplants are under investigation as a possible cure. Recently, treatments that are more specific in modifying the particular subset of the immune cells (e.g. B- or T- cells) or cytokine proteins they secrete have been gaining attention. Research into new treatments has recently been accelerated by genetic discoveries, especially mapping of the human genome. According to a June 2006 market analysis report by Datamonitor, treatment for SLE could be on the verge of a breakthrough as there are numerous late-Phase trials currently being carried out. There have been promising advances in the area of stem cell research implicating a treatment with adult stem cells being harvested from the patients themselves.

Prevention

Lupus is not understood well enough to be prevented, but when the disease develops, quality of life can be improved through flare prevention. The warning signs of an impending flare include increased fatigue, pain, rash, fever, abdominal discomfort, headache and dizziness. Early recognition of warning signs and good communication with a doctor can help individuals with lupus remain active, experience less pain and reduce medical visits.

Prevention of complications during pregnancy

While most infants born to mothers with lupus are healthy, pregnant mothers with SLE should remain under a doctor's care until delivery. Neonatal lupus is rare, but identification of mothers at highest risk for complications allows for prompt treatment before or after birth. In addition, SLE can flare during pregnancy and proper treatment can maintain the health of the mother for longer. Women pregnant and known to have the antibodies for anti-Ro (SSA) or anti-La (SSB) should have echocardiograms during the 16th and 30th weeks of pregnancy to monitor the health of the heart and surrounding vasculature.^[4]

Prognosis

In the 1950s, most patients diagnosed with SLE lived fewer than five years. Advances in diagnosis and treatment have improved survival to the point where over 90% of patients now survive for more than ten years and many can live relatively asymptomatically. The most common cause of death is infection due to immunosuppression as a result of medications used to manage the disease. Prognosis is normally worse for men and children than for women. Fortunately, if symptoms are present after age 60, the disease tends to run a more benign course. The ANA is the most sensitive screening test while Anti-Sm (Anti Smith) is the most specific. The ds-DNA (double-stranded DNA) antibody is also fairly specific and often fluctuates with disease activity. The ds-DNA titer is therefore sometimes useful to diagnose or monitor acute flares or response to treatment.

Epidemiology

Previously believed to be a rare disease, Lupus has seen an increase in awareness and education since the 1960s. This has helped many more patients get an accurate diagnosis making it possible to estimate the number of people with lupus. In the United States alone, it is estimated that between 270,000 and 1.5 million people have lupus, making it more common than cystic fibrosis or cerebral palsy. The disease affects both females and males, though young women are diagnosed nine times more often than men. SLE occurs with much greater severity among African-American women, who suffer more severe symptoms as well as a higher mortality rate.^[31] Worldwide, a conservative estimate states that over 5 million people have lupus.

Although SLE can occur in anyone at any age, it is most common in women of childbearing age. It affects 1 in 4000 people in the United States, with women becoming afflicted far more often than men. The disease appears to be more prevalent in women of African, Asian, Hispanic and Native American origin but this may be due to socioeconomic factors. People with relatives who suffer from SLE, rheumatoid arthritis or thrombotic thrombocytopenic purpura are at a slightly higher risk than the general population.

History

Medical historians have theorized people with porphyrias (a disease that shares many symptoms with Lupus) generated folklore stories of vampires and werewolves due to the photosensitivity, scarring, hair growth and porphyrin brownish-red stained teeth in severe recessive forms of porphyria or combinations of the disorders known as dual, homozygous or compound heterozygous porphyrias.

The history of lupus erythematosus can be divided into three periods: the classical, neoclassical, and modern. The classical period began when the disease was first recognized in the Middle Ages and saw the description of the dermatological manifestation of the disorder. The term lupus is attributed to the 12th century physician Rogerius, who used it to describe the classic malar rash. The neoclassical period was heralded by Móric Kaposi's recognition in 1872 of the systemic manifestations of the disease. The modern period began in 1948 with the discovery of the LE cell (the Lupus Erythematosus cell, a misnomer as it occurs with other diseases as well) and is characterised by advances in our knowledge of the pathophysiology and clinical-laboratory features of the disease, as well as advances in treatment.

Useful medication for the disease was first found in 1894, when quinine was first reported as an effective therapy. Four years later, the use of salicylates in conjunction with quinine was noted to be of still greater benefit. This was the best available treatment to patients until the middle of the twentieth century, when Hench discovered the efficacy of corticosteroids in the treatment of SLE.

Origins of "Lupus Erythematosus"

There are several explanations ventured for the term lupus erythematosus. Lupus is Latin for wolf, and 'erythro' is derived from ερυθρός, Greek for "red". All explanations originate with the reddish, butterfly-shaped malar rash that the disease classically exhibits across the nose and cheeks.

1. In various accounts, some doctors thought the rash resembled the pattern of fur on a wolf's face.
2. In other accounts doctors thought that the rash, which was often more severe in earlier centuries, created lesions that resembled wolf bites or scratches.
3. Another account claims that the term "Lupus" did not come from Latin at all, but from the term for a French style of mask which women reportedly wore to conceal the rash on their faces. The mask is called a "loup", French for "Wolf"
4. Another common explanation for the term is that the disease's course involves repeated attacks like those of a voracious predator, leaving behind the red blotches.